This proposal describes the rational design and synthesis of substrates capable of recognizing DNA with a high degree of specificity for base-pair sequence and molecular conformation. The goal is to define the minimum requirements for DNA-binding proteins to recognize a specific base-pair sequence by using only those portions of the protein which are believed to be responsible for site-selective contacts. A portocol is established for the logical design and synthesis of a number of novel sugar-derived water-soluble "rigid" molecules which are capable of extending the distance required for each termini to reside in adjacent major- (or minor) grooves of B-DNA (33 - 34 Angstroms). The synthesis involves stereoselective C- glycosidations to construct the C-1-C-4' bond of deoxo- polysaccharides and 3,3 sigmatropic rearrangements for the construction of transoxo bipyranose derivatives. The target C- polysaccharides are "capped" with small peptides at each termini (Ca1 - Cg4) to afford C-glycoproteins of defined configuration. Several modes of binding are presented which are controlled by the symmetry of the terminal peptides and the size of the C- polysaccharide connecting them. Besides obtaining information on the parameters of binding recognition, the synthetic recognition fragments offer an array of existing multidisciplinary applications. These include the design of restriction endonucleases, their use as probes and mimics of other DNA-binding proteins and finally their potential as DNA- targeted antitumor agents.